The project described in this application combines modern epidemiologic and immunohistochemical techniques (a) to determine the cellular localizations, intercellular distributions, and levels of carcinogen-metabolizing enzymes within human breast and prostate tissue and (b) to explore the environmental correlates of these enzyme patterns in relationship to the risk of breast and prostate cancer. Immunohistochemical techniques will be employed to examine cytochromes P-450, NADPH-Cytochrome c (p-450) reductase, epoxide hydrolase, and glutathione S-transferases at the light microscopic level within histologically normal breast and prostate tissue obtained from patients undergoing surgical procedures for cancer diagnosis and treatment. Subjects without benign or malignant neoplasms also undergoing surgery of these organs will serve as controls in these studies. Cases and controls will have questionnaires administered concerning relevant cancer risk factors and potential environmental correlates of the presence and levels of carcinogen-metabolizing enzymes. Differences in these enzymes between cases and controls will be determined, and any differences found will be reconciled with the epidemiologic variables at hand. For women with breast cancer, carcinogen-metabolizing enzymes will also be examined in specimens of breast skin, and findings of these examinations will be compared to respective findings in breast parenchyma. The studies described for this project will explore, in some instances for the first time, human carcinogen-metabolizing enzymes in situ, their potential associations with clinical cancer risk, and their associations with confirmed or putative epidemiologic risk factors and selected environmental exposures.